title: Decreased bone mineral density in subjects carrying familial defective apolipoprotein B-100.
abstract: BACKGROUND
  Although numerous epidemiologic studies have documented associations between osteoporosis and cardiovascular disease, the mechanisms underlying this association remain to be clarified. One hypothesis is that hyperlipidemia may be a common predisposing factor to both atherosclerotic heart disease and bone fragility.
  
  
  OBJECTIVE
  To evaluate this, we compared bone mineral density (BMD) between subjects with and without the R3500Q APOB mutation, the cause of familial defective apolipoprotein B-100, which has been previously shown to markedly increase low-density lipoprotein cholesterol (LDL-C). We hypothesized that R3500Q carriers would have lower BMD due to lifetime, elevated LDL-C.
  
  
  METHODS
  This was a a cross-sectional study in the Old Order Amish (OOA) population.
  
  
  METHODS
  The R3500Q APOB mutation is present at a high frequency (∼6% vs <0.5%) in the OOA population due to a founder effect. Therefore, we conducted analysis on 1097 Amish individuals of whom 125 were R3500Q carriers.
  
  
  METHODS
  BMD was measured by dual-energy x-ray absorptiometry.
  
  
  RESULTS
  After adjusting for age, age(2), sex, body mass index, and family structure, carriers for the Q risk allele had significantly lower BMD than noncarriers at the femoral neck (P = .037), lumbar spine (P = .035) and whole body (P = .016). Adjusting for LDL-C attenuated the association between R3500Q genotype and BMD but did not completely explain the relationship. Subgroup analyses showed no significant interactions with sex, age, or presence of metabolic syndrome.
  
  
  CONCLUSIONS
  These results use the unique genetic architecture of the OOA population to provide a novel line of evidence supporting a causal role for elevated LDL-C in lowering BMD.
authors.affiliation: Baltimore, MD 21201. lyerges@medicine.umaryland.edu.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yerges-Armstrong
authors.forename: Haiqing
authors.initials: H
authors.lastname: Shen
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Streeten
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D061365:Amish; D053299:Apolipoprotein B-100 / Q000235:genetics* / Q000378:metabolism; D015519:Bone Density; D001862:Bone Resorption / Q000209:etiology*; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D018703:Founder Effect; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D010414:Pennsylvania; D017354:Point Mutation; D055815:Young Adult
chemical_list: D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL